Comparison of various solubility-enhancing techniques for enhanced solubility and oral bioavailability of water-insoluble revaprazan

Abstract

The basal idea of this research was to compare divergent strategies to enhance the solubility of aqueous-insoluble revaprazan hydrochloride in order to select the finest strategy which causes enhancement in the oral bioavailability of the drug. While using the optimized ratio of revaprazan hydrochloride/HPMC/Cremophor A25 (5/1.4/5.6 w/w/w), the solvent wetted solid dispersion (SWSD) and surface-attached solid dispersion (SASD) were fabricated. The solid self nano-emulsifying drug delivery system (SNEDDS) was formulated with revaprazan hydrochloride/Peceol/Tween 80/Labrasol/Dextran at the ratio of 10/15/55/30/5 (w/v/v/v/w). The gelatin microcapsule was optimized at the weight ratio of 1/2 with revaprazan hydrochloride/Gelatin. Moreover, inclusion compound were devised with revaprazan hydrochloride/HP-β-CD at the selected ratio of 2.5/8.77 (w/w). Spray drying was opted to fabricate all five solid state formulations. The physicochemical properties were investigated by the SEM, DSC, PXRD and FTIR. Furthermore, in comparison to the drug powder the aqueous solubility, dissolution and pharmacokinetics were performed. It was observed from the obtained solubility screening results that, all the selected formulations gave a significant enhancement in the solubility of water-insoluble revaprazan hydrochloride. The crystal lattice of the drug was preserved in the SASD; however, it was evident that in the SWSD, the crystallinity of the drug was altered. On the other hand, in solid SNEDDS, gelatin microcapsule and inclusion compound it was confirmed that the drug crystal form was completely converted to the amorphous form. The solubility, dissolution and the oral bioavailability of the drug in the fabricated formulations were amplified in the order of solvent wetted SD > SNEDDS > surface-attached SD > inclusion compound > gelatin microcapsule > drug powder. Amidst the modified drug delivery system accustomed in this research, solvent wetted solid dispersion displayed the highest and solid SNEDDS showed the second-highest oral bioavailability of revaprazan hydrochloride, respectively.